rs2523607

Positions:

• chr6-31355013-T-A
• chr6-31355013-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005514.8(HLA-B):​c.1012+94A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.084 (617 hom., cov: 8)
  • Exomes 𝑓: 0.11 (5626 hom.)
  • Failed GnomAD Quality Control
• Consequence: HLA-B NM_005514.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.45

Genes affected

HLA-B (HGNC:4932): (major histocompatibility complex, class I, B) HLA-B belongs to the HLA class I heavy chain paralogues. This class I molecule is a heterodimer consisting of a heavy chain and a light chain (beta-2 microglobulin). The heavy chain is anchored in the membrane. Class I molecules play a central role in the immune system by presenting peptides derived from the endoplasmic reticulum lumen. They are expressed in nearly all cells. The heavy chain is approximately 45 kDa and its gene contains 8 exons. Exon 1 encodes the leader peptide, exon 2 and 3 encode the alpha1 and alpha2 domains, which both bind the peptide, exon 4 encodes the alpha3 domain, exon 5 encodes the transmembrane region and exons 6 and 7 encode the cytoplasmic tail. Polymorphisms within exon 2 and exon 3 are responsible for the peptide binding specificity of each class one molecule. Typing for these polymorphisms is routinely done for bone marrow and kidney transplantation. Hundreds of HLA-B alleles have been described. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.125 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLA-B	NM_005514.8	c.1012+94A>T		intron_variant		ENST00000412585.7	NP_005505.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HLA-B	ENST00000412585.7	c.1012+94A>T		intron_variant			NM_005514.8	ENSP00000399168	P1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 5259 AN: 62516 Hom.: 614 Cov.: 8 FAILED QC

Gnomad AFR AF: 0.0822

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.0499

Gnomad ASJ AF: 0.0833

Gnomad EAS AF: 0.00294

Gnomad SAS AF: 0.0646

Gnomad FIN AF: 0.0629

Gnomad MID AF: 0.0426

Gnomad NFE AF: 0.0983

Gnomad OTH AF: 0.0773

GnomAD4 exome AF: 0.106 AC: 33241 AN: 313138 Hom.: 5626 Cov.: 4 AF XY: 0.106 AC XY: 17662 AN XY: 165856

Gnomad4 AFR exome AF: 0.128

Gnomad4 AMR exome AF: 0.0455

Gnomad4 ASJ exome AF: 0.0999

Gnomad4 EAS exome AF: 0.00176

Gnomad4 SAS exome AF: 0.113

Gnomad4 FIN exome AF: 0.0802

Gnomad4 NFE exome AF: 0.119

Gnomad4 OTH exome AF: 0.124

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0842 AC: 5267 AN: 62530 Hom.: 617 Cov.: 8 AF XY: 0.0792 AC XY: 2364 AN XY: 29844

Gnomad4 AFR AF: 0.0825

Gnomad4 AMR AF: 0.0499

Gnomad4 ASJ AF: 0.0833

Gnomad4 EAS AF: 0.00295

Gnomad4 SAS AF: 0.0663

Gnomad4 FIN AF: 0.0629

Gnomad4 NFE AF: 0.0983

Gnomad4 OTH AF: 0.0761

Alfa AF: 0.0537 Hom.: 61

Asia WGS AF: 0.0330 AC: 115 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	8.1
DANN	Benign	0.50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2523607; hg19: chr6-31322790;